The dystonic rat is a model of inherited movement disorders discovered in Sprague-Dawley rats. The dt rat displays sustained, twisting movements in the waking state, starting on postnatal days 9-10 following a period of apparently normal development. The movements seen in the dt rat are analogous to those that characterize the disease torsion dystonia in man. Inheritance in the rat model follows an autosomal recessive pattern. As in the human disease, routine histopathological study reveals no evidence of morphological lesions or degenerative processes in the central or peripheral nervous system of rats displaying advanced clinical signs. However, in the rat model application of neurochemical, morphological and psychopharmacological techniques to study noradrenergic, dopaminergic, cholinergic, and GABAergic systems in brain has revealed specific abnormalities including increased GAD activity in the deep cerebellar nuclei, increased steady state levels of cerebellar norepinephrine and decreased cerebellar cGMP. These are not generalized abnormalities in noradrenergic or GABAergic systems. Other evidence of pathology in the cerebellum includes the presence of tubular, honeycombed inclusions of axons seen in electron micrographs. The dt rats are also less sensitive to the tremorogenic effects of harmaline, a drug that acts on one of the major cerebellar afferent systems. The proposed studies are designed to continue a systematic interdisciplinary investigation of the dt rat. Emphasis is given to studies that are designed to provide explanations for previously documented neurochemical and psychopharmacological abnormalities. Specifically, studies are proposed to assess the function to major components of cerebellar circuitry and to determine their relationship to dystonia. Neurochemical, electrophysiological and anatomical techniques will be used. The proposed studies are expected to lead to increased understanding of human torsion dystonia and normal development of motor systems.